In the field of treatment of bronchial diseases, and also of other diseases in which medication can be given via the airways, it is known not only to atomize solutions or suspensions into inhalable aerosols but also to administer powdered medicaments. Many examples of such medicaments are described in the literature, and of these we refer purely by way of illustration to WO 93/11773, EP 0 416 950 A1 and EP 0 416 951 A1.
A customary form of administration in this connection is delivery via an inhalation device (inhaler).
Known inhalers for powdered pharmaceuticals include those for administration of a single dose and also inhalation devices which have a reservoir for a plurality of pharmaceutical doses. In this connection, it is known either to provide separate storage spaces for each individual dose or to provide one single receiving space for receiving a multiplicity of doses of a medicament.
Known inhalers in which a multiplicity of individual doses are provided in separate storage spaces include those in which individual areas of the inhaler are each filled with a pharmaceutical dose.
An example of such an inhaler is described in U.S. Pat. No. 5,301,666. However, it is also known to accommodate a multiplicity of pharmaceutical powder doses in separate areas, so-called blister packs. An example of such a blister pack for use with an inhaler is described in DE 44 00 083 C2. Such a blister pack, which is designed at the same time as a disposable inhaler, is described for example in DE 44 00 084 A1.
An inhalation device into which blister packs can be inserted, which each have separate storage spaces for individual doses of a powdered pharmaceutical and which can be emptied one after another with the aid of the inhalation device, is described, for example, in DE 195 23 516 C1.
Many examples of inhalers with a storage space for a multiplicity of pharmaceutical doses are described in the prior art. One example with an exchangeable storage container is described in German Patent Specification 846 770, and another in WO 95/31237.
An important problem with inhalation systems in which a multiplicity of doses of a medically active substance are accommodated in a common storage space concerns the apportioning of an individual dose for one individual inhalation. In this connection, a great many solutions have been proposed, for example those which are described in U.S. Pat. No. 2,587,215 and U.S. Pat. No. 4,274,403. Other types of arrangements for metering an individual dose of pharmaceutical powder from a storage space for a multiplicity of pharmaceutical doses are described in WO 92/09322, WO 93/16748 and DE 35 35 561 C2 and in GB 2 165 159 A. An exchangeable cartridge for receiving a multiplicity of doses of a pharmaceutical powder with an integrated metering slide is known from DE 195 22 415 A1.
Another important problem with inhalation of pharmaceutical powders concerns the breakdown of the galenic powder formulations into particles which can access the lungs. The active substances administered in this way are generally combined with vehicles in order to achieve a reasonable dosing capacity of the medically active substance and to set further properties of the pharmaceutical powder, which for example can influence the storage life.
Proposed solutions concerning the designs of powder inhalers with which particles which can access the lungs are intended to be made available in an air stream for inhalation are described for example in EP 0 640 354 A2, U.S. Pat. No. 5,505,196, U.S. Pat. No. 5,320,714, U.S. Pat. No. 5,435,301, U.S. Pat. No. 5,301,666, DE 195 22 416 A1 and WO 97/00703. Proposals are also known to use auxiliary energy to generate the air stream, for example in ZA-A 916741.
In the drug treatment of diseases, it is generally known to use different pharmacodynamically active substances together. In medicaments in tablet form or ointment form, this has been known for a long time and is customary practice. From the pharmacological point of view, it must simply be ensured that the active substances or galenic substances do not negatively influence each other, both in terms of the effect on the body and in terms of absorption.
Also in the case of medicaments for inhalation in powder form, it is known to combine active substances by administering prepared active substance mixtures. Corresponding proposals are found in EP 0 416 951 A1 and WO 93/11773, for example for combination of salmeterol and fluticasone or formoterol and budesonide. Nevertheless, when preparing active substance mixtures in the form of loose powders, the problem remains that chemical or physical reactions of the active substances in the mixtures can cause these to change, particularly during a prolonged period of storage, which can lead to a decreased effect, inhomogeneity of the mixture, which can lead to dose variations or to undesired side effects.
To avoid such disadvantages, the pharmacodynamically active substances are therefore often administered sequentially, i.e. separately one after the other. In this connection, different administration systems are also often used for different active substances. This not only makes administration more difficult for the user, causing mix-ups, administration errors and poor compliance, but also makes such medication impractical in certain diseases. These diseases can include in particular those in which the symptoms occur in attacks and where such attacks mean that the patient's coordination and handling ability are limited by physical or psychological deficits. A typical example of this is asthma attacks.
The object of the invention is therefore to improve known systems for administration of powdered pharmaceuticals.
According to the invention, this object is achieved by a storage system for powdered pharmaceuticals, in particular for use or integration in a powder inhaler, for receiving a multiplicity of doses of at least one medically active substance, with at least two storage spaces which are separate from each other and are each intended to hold a multiplicity of doses of a medically active substance.
With the system according to the invention, it is possible to make available pharmacodynamically active substances in the form of powdered pharmaceuticals in separate storage spaces for a multiplicity of doses, yet still achieve coordinated dosing and administration of the active substances in combination, without making additional demands on the patient or medical career, compared with a conventional inhalation of an individual pharmaceutical powder, and without additional handling requirements.
By combining separate storage spaces in the form of individual cartridges containing the same powdered pharmaceutical, the invention also makes it possible for the doctor to provide a dose very precisely adapted to the patient, without requiring a correspondingly large number of different cartridges with different metering devices.
The storage system is particularly expediently characterized in that the storage system comprises a pharmaceutical powder cartridge system for use in a medical administration device (inhaler).
For a particularly good combination of active substances, it is advantageous if the system further comprises a device for approximately simultaneous administration of pharmaceutical doses from at least two of the separate storage spaces.
In an advantageous embodiment, the pharmaceutical powder cartridge system comprises a pharmaceutical powder cartridge which has at least two storage chambers. In this case, it is expedient if the pharmaceutical powder cartridge has a metering device, and if the metering device has, for each of the storage chambers, a metering chamber for apportioning a predetermined quantity of each medically active substance provided in the storage chambers.
Particularly in the case of fixed integration in a powder inhaler, it can be advantageous if the pharmaceutical powder cartridge system has a device for bringing together the quantities of substance apportioned by the metering chambers.
For a freer combination of the active substances or dose quantities by a doctor or pharmacist, it may also be expedient, however, if the storage system comprises a pharmaceutical powder cartridge system with at least two pharmaceutical powder cartridges which each have at least one storage chamber.
In this connection, it is especially advantageous if each pharmaceutical powder cartridge has a metering device, and if each metering device has, for each of the storage chambers, a metering chamber for apportioning a predetermined quantity of each medically active substance provided in the storage chambers of the pharmaceutical powder cartridges.
Particularly if the pharmaceutical powder cartridge system with different active substance combinations is intended to be used sequentially in an inhaler, it is expedient, in order to avoid interactions of the powdered medicaments, if the pharmaceutical powder cartridge system has a device for bringing together the quantities of substance apportioned by the metering chambers.
In an advantageous embodiment, the metering devices can be coupled together.
For especially good handling, it is advantageous if the pharmaceutical powder cartridges can be coupled together mechanically.
A particularly good safeguard against incorrect medication can be obtained if, on active surfaces serving to couple the pharmaceutical powder cartridges together, the pharmaceutical powder cartridges also have indexing means which permit coupling only of pharmaceutical powder cartridges intended for this purpose. In this case, it is expedient if the indexing means have elevations and depressions which permit coupling only of pharmaceutical powder cartridges which are intended for this purpose and which have matching elevations and depressions, in particular if the elevations and depressions are arranged in the form of a matrix.
For combining cartridges for the pharmaceutical powder cartridge system according to the invention, for example by a pharmacist, it is expedient if, on their active surfaces serving to couple the pharmaceutical powder cartridges together, the pharmaceutical powder cartridges also have locking means which permit coupling of pharmaceutical powder cartridges intended for this purpose. An especially effective safeguard against manipulation by unauthorized persons or to prevent refilling of the pharmaceutical powder cartridges can be obtained if the locking means are designed in such a way that the coupled pharmaceutical powder cartridges cannot be separated from each other again without damage.
For handling by the patient, it is advantageous if the pharmaceutical powder cartridge system also has a device for indicating the quantity of pharmaceutical doses remaining in the storage chambers or removed from the storage chambers, in particular if the pharmaceutical powder cartridges can be coupled to one another and to the device for indicating the quantity of pharmaceutical doses remaining in the storage chambers or removed from the storage chambers and/or if the pharmaceutical powder cartridge system has, for each of the storage chambers, a device for indicating the quantity of pharmaceutical doses remaining in the storage chambers or removed from the storage chambers.
It is especially favourable, from the point of view of production technology, if the pharmaceutical powder cartridge system comprises two or more pharmaceutical powder cartridges which, without the locking and indexing means, are identical, show mirror-image symmetry or point-symmetry.
For a particularly versatile use, it is advantageous if the metering devices of the individual pharmaceutical powder cartridges have metering cavities of identical or different volume.
The invention can be used particularly cost-effectively in an inhaler for powdered pharmaceuticals with a pharmaceutical powder cartridge system according to one of the preceding claims as an integral part or as an exchangeable part.